Tissue Formation and Vascularization in Anatomically Shaped Human Joint Condyle Ectopically in Vivo

Scale-up of bioengineered grafts toward clinical applications is a challenge in regenerative medicine. Here, we report tissue formation and vascularization of anatomically shaped human tibial condyles ectopically with a dimension of 20 15 15mm3. A composite of poly-ɛ-caprolactone and hydroxyapatite was fabricated using layer deposition of three-dimensional interlaid strands with interconnecting microchannels (400μm) and seeded with human bone marrow stem cells (hMSCs) with or without osteogenic differentiation. An overlaying layer (1mm deep) of poly(ethylene glycol)-based hydrogel encapsulating hMSCs or hMSC-derived chondrocytes was molded into anatomic shape and anchored into microchannels by gel infusion. After 6 weeks of subcutaneous implantation in athymic rats, hMSCs generated not only significantly more blood vessels, but also significantly larger-diameter vessels than hMSC-derived osteoblasts, although hMSC-derived osteoblasts yielded mineralized tissue in microchannels. Chondrocytes in safranin-O-positive glycosaminoglycan matrix were present in the cartilage layer seeded with hMSC-derived chondrogenic cells, although significantly more cells were present in the cartilage layer seeded with hMSCs than hMSC-derived chondrocytes. Together, MSCs elaborate substantially more angiogenesis, whereas their progenies yield corresponding differentiated tissue phenotypes. Scale up is probable by incorporating a combination of stem cells and their progenies in repeating modules of internal microchannels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78100/1/ten.tea.2008.0653.pd